Cerebrospinal fluid levels of NfM in relation to NfL and pNfH as prognostic markers in amyotrophic lateral sclerosis

Abstract

AbstractObjectiveTo evaluate the prognostic potential of neurofilament medium chain (NfM) in CSF from patients with ALS and explore its relationship with the extensively studied neurofilament light chain (NfL) and phosphorylated heavy chain (pNfH).MethodCSF levels of NfL, NfM, and pNfH were analysed in 235 samples from patients with ALS, ALS mimics, and healthy controls in a well-characterized cohort from Karolinska ALS Clinical Research Centre in Stockholm, Sweden. NfM levels were analysed using an antibody-based suspension bead-array and NfL and pNfH levels were measured using standard ELISA. Clinical data, including ALS Revised Functional Rating Scale (ALSFRS-R), and survival outcomes were utilized for disease progression estimations.ResultIncreased NfM levels were observed in patients with ALS compared with mimics and healthy controls, consistent with the results observed for NfL and pNfH. Similar to NfL and pNfH, significant associations of NfM levels with disease progression were found, with higher levels in fast progressors compared with slow progressors, both in total progression and the ALSFRS-R subscores. For all neurofilaments, higher survival probability was observed for patients with low CSF levels. Additionally, all three proteins showed similar predictive performance for disease progression rates (AUC 0.85-0.86). Although there was no statistical difference between the curves, combining them slightly improved the performance (AUC 0.86-0.87).ConclusionBased on this cross-sectional study, the prognostic value provided by NfM aligns with the more established markers, NfL and pNfH. However, additional investigations with independent cohorts and longitudinal studies are needed to further explore the potential added value of NfM.